Ethyl 2-(4-benzyl-3-methyl-6-oxo-1,6-dihydropyridazin-1-yl)acetate: crystal structure and Hirshfeld surface analysis

In the title molecule, the oxopyridazinyl ring is N-bound to an ethylacetate group with benzyl and methyl groups substituted at adjacent C atoms. In the molecular packing, methylene-C—H⋯O(ring carbonyl) and N(pyridazinyl) interactions result in the formation of a supramolecular tape along the a-axis direction.


Chemical context
Pyridazin-3(2H)-ones are pyridazine derivatives, being constructed about a six-membered ring which contains two adjacent nitrogen atoms, at positions one and two, and with a carbonyl group at position three. The interest in these nitrogen-rich heterocyclic derivatives arises from the fact that they exhibit a number of promising pharmacological and biological activities. These include anti-oxidant (Khokra et al., 2016), anti-bacterial and anti-fungal (Abiha et al. 2018), anti-cancer (Kamble et al. 2017), analgesic and anti-inflammatory (Ibrahim et al. 2017), anti-depressant (Boukharsa et al. 2016) and anti-ulcer activities (Yamada et al., 1981). In addition, a number of pyridazinone derivatives have been reported to have potential as agrochemicals, for example as insecticides (Nauen & Bretschneider, 2002), acaricides (Igarashi & Sakamoto, 1994) and herbicides (Azaari et al., 2016). Given the interest in this class of compound and the paucity in structural data (see Database survey), the crystal and molecular structures of the the title pyridazin-3(2H)-one derivative, (I), has ISSN 2056-9890 been undertaken along with an analysis of the calculated Hirshfeld surface in order to gain further insight into the molecular packing.

Structural commentary
The molecular structure of (I), Fig. 1, comprises a central oxopyridazinyl ring connected to an ethylacetate group at the N1 atom, a methyl group at the C2 position and a benzyl residue at the C3 atom. The oxopyridazinyl ring is almost planar, having an r.m.s. deviation of 0.0047 Å for the ring atoms, with the maximum deviation from the ring being 0.0072 (6) Å for the C3 atom; the O1 atom lies 0.0260 (13) Å out of the plane in the same direction as the C3 atom. The ethyl acetate group is close to planar with the r.m.s. deviation for the O2,O3,C12-C16 atoms being 0.0476 Å [the maximum deviation from the least-squares plane is 0.0711 (7) Å for the O3 atom]. The dihedral angle between the two mentioned planes is 77.48 (3) , indicating an approximately orthogonal relationship. The ethyl acetate group lies to one side of the central plane, as seen in the value of the N2-N1-C13-C14 torsion angle of 104.34 (9) . The benzyl ring forms a dihedral angle of 76.94 (3) with the central ring, also indicating an approximately orthogonal relationship but, in this case, the benzyl ring is bisected by the pseudo mirror plane passing through the oxopyridazinyl ring. Consistent with this, the pendant groups form a dihedral angle of 69.74 (3) . Within the ester group, it is the carboxylate-O3 atom that is directed away from the oxopyridazinyl ring so that the carbonyl-O1 and O2 atoms are proximate, at least to a first approximation.

Figure 2
Supramolecular association in the crystal of (I): (a) a view of the supramolecular tape along the a-axis direction sustained by methylene-C13-HÁ Á ÁO1(ring carbonyl) or N2(pyridazinyl) interactions shown as orange and blue dashed lines, respectively, and (b) a view of the unit-cell contents shown in projection down the a axis.

Hirshfeld surface analysis
The Hirshfeld surfaces calculated for (I) were performed in accord with recent studies (Tan et al., 2019) in order to provide complementary information on the influence of short interatomic contacts on the molecular packing. On the Hirshfeld surfaces mapped over d norm in Fig. 3(a), the C-HÁ Á ÁN contact involving the methylene-H13A and pyridazinyl-N2 atoms are represented as bright-red spots on the surface. The diminutive red spots appearing near the methylene-H13B and carbonyl-O1 atoms indicate the weak C-HÁ Á ÁO contact, Fig. 3(a) and (b). The intense blue and red regions corresponding to positive and negative electrostatic potentials on the Hirshfeld surfaces mapped over electrostatic potential in Fig. 4 also represent the donors and acceptors of the above intermolecular interactions, respectively. The influence of the short interatomic OÁ Á ÁH/HÁ Á ÁO, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts, as summarized in Table 2, are viewed as the faint-red spots on the d norm -mapped Hirshfeld surfaces in Fig. 3. The environment of short interatomic OÁ Á ÁH/HÁ Á ÁO, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts about the reference molecule within d norm mapped Hirshfeld surface illustrating weak intermolecular interactions are shown in the views of Two views of the Hirshfeld surface for (I) mapped over d norm in the range À0.085 to +1.271 arbitrary units.

Figure 4
Two views of the Hirshfeld surface mapped over the electrostatic potential in the range À0.076 to +0.039 atomic units. The red and blue regions represent negative and positive electrostatic potentials, respectively.

Figure 5
Two views of Hirshfeld surface mapped over d norm in the range À0.085 to +1.271 arbitrary units showing significant short inter atomic OÁ Á ÁH/ HÁ Á ÁO, CÁ Á ÁH/HÁ Á ÁC and CÁ Á ÁC contacts by sky-blue, yellow and black dotted lines, respectively. illustrated in Fig. 6(b)-(f); the percentage contribution from different interatomic contacts to the Hirshfeld surfaces of (I) are summarized in Table 3. In the fingerprint plot delineated into HÁ Á ÁH contacts shown in Fig. 6(b), having the greatest contribution, i.e. 52.2%, to the Hirshfeld surface, a pair of beak-shaped tips at d e + d i $2.3 Å reflect the short interatomic contact between the methyl-H5C and H16C atoms, Table 2. The fingerprint plot delineated into OÁ Á ÁH/HÁ Á ÁO contacts in Fig. 6(c) demonstrates two pairs of adjoining short tips at d e + d i $2.5 and 2.6 Å , together with the green aligned points in the central region, which are indicative of weak C-HÁ Á ÁO contacts present in the crystal. The pair of long spikes at d e + d i $2.5 Å in the fingerprint plot delineated into NÁ Á ÁH/HÁ Á ÁN contacts of Fig. 6(d), are the result of a potential C-HÁ Á ÁN interaction involving the methylene-C13-H13A and pyridazinyl-N2 atoms. The short interatomic CÁ Á ÁH/HÁ Á ÁC contacts as summarized in Table 2 are represented by a pair of forcepslike and parabolic tips a d e + d i $2.7 and 2.8 Å , respectively in Fig. 6(e). The presence of a weakcontact between the oxopyridazinyl and phenyl rings is reflected in the thick arrowlike tip at d e + d i $3.4 Å in the fingerprint plot delineated into CÁ Á ÁC contacts of Fig. 6(f), specifically the short interatomic C2Á Á ÁC9 contact, Table 2, and the small but notable, i.e. 2.3%, contribution from CÁ Á ÁN/NÁ Á ÁC contacts to the Hirshfeld surface.

Database survey
The most closely related structure to (I) in the crystallographic literature is compound (II) whereby the benzyl group of (I) is substituted by a (5-chloro-1-benzofuran-2-yl)methyl) group (Aydın et al., 2007). The structure of (II) presents the same features as for (I) but, with the ester-carbonyl atom directed away from the ring carbonyl group as highlighted in the overlay diagram of Fig. 7.

Synthesis and crystallization
A mixture of 3-benzylidene-4-oxopentanoic acid (0.05 mol) and hydrazine hydrate (0.1 mol) in ethanol (100 ml) was refluxed for 2 h. The precipitate formed was filtered off and recrystallized from acetone to obtain the 5-benzyl-6-methylpyridazin-3(2H)-one precursor. To this pyridazine (0.05 mol) was added potassium carbonate (0.1 mmol), tetrabutylammonium bromide (0.01 mmol) and 2-ethyl bromoacetate (0.1 mol) in dimethylformamide (20 ml). The mixture was stirred for 24 h at room temperature. At the end of the reaction, the solution was filtered and the solvent evaporated under reduced pressure. The residue was washed with water and methylenechloride. The solvent was removed and colourless blocks of (I) were obtained by recrystallization of the product from its acetone solution.  Table 2 Summary of short interatomic contacts (Å ) in (I).

Special details
Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 15 sec/frame. Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.